期刊
REDOX BIOLOGY
卷 30, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.redox.2019.101416
关键词
GSTpi; VE-Cadherin; Src/VE-Cadherin pathway; S-Glutathionylation of Src; Endothelial barrier function
资金
- Natural Science Foundation of China [31571166, 81913498, 81602733, 81973498, 81771703, 81902706, 81471557, 81671565]
- Outstanding Youth Fund of Jiangsu Province [BK20140049]
- Priority Academic Program Development of Jiangsu Higher Education Institution (PADD)
GSTpi is a Phase II metabolic enzyme which is originally considered as an important facilitator of cellular detoxification. Here, we found that GSTpi stabilized VE-cadherin in endothelial cell membrane through inhibiting VE-cadherin phosphorylation and VE-cadherin/catenin complex dissociation, and consequently maintained endothelial barrier function. Our findings demonstrated a novel mechanism that GSTpi inhibited VE-cadherin phosphorylation through suppressing the activation of Src/VE-cadherin pathway. Mass spectrometry analysis and molecular docking showed that GSTpi enhanced Src S-glutathionylation at Cys185, Cys245, and Cys400 of Src. More important, we found that GSTpi promoted S-glutathionylation of Src was essential for GSTpi to inhibit Src phosphorylation and activation. Furthermore, in vivo experiments indicated that AAV-GSTpi exerted the protective effect on pulmonary vessel permeability in the animal model of acute lung injury. This study revealed a novel regulatory effect of GSTpi on vascular endothelial barrier function and the importance of S-glutathionylation of Src induced by GSTpi in the activation of Src/VE-cadherin pathway.
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